Changes in intestinal microbiota in HIV-1-infected subjects following cART initiation: influence of CD4+ T cell count

The roles of immunodeficiency and combined antiretroviral therapy (cART) in shaping the gut microbiota in HIV-1-infected subjects (HISs) have not been described thoroughly by time-series investigations. In this study, 36 antiretroviral-naïve HISs were enrolled to prospectively assess alterations in the fecal microbiota and plasma markers of microbial translocation and inflammation with cART. At baseline, the species α-diversity of the fecal microbiota was significantly lower in HISs with a CD4⁺ T cell count &lt;300/mm³ than in HISs with a CD4⁺ T cell count &gt;300/mm³ (Shannon index: Median 2.557 vs. 2.981, <i>P</i> = 0.006; Simpson index: Median 0.168 vs. 0.096, <i>P</i> = 0.004). Additionally, the baseline α-diversity indices correlated with CD4⁺ T cell counts (Shannon index: <i>r</i> = 0.474, <i>P</i> = 0.004; Simpson index: <i>r</i> = −0.467, <i>P</i> = 0.004) and the specific plasma biomarkers for microbial translocation and inflammation. After cART introduction, the species α-diversity of fecal microbiota in HISs with CD4⁺ T cell counts &lt;300/mm³ was significantly restored (Shannon index: Median 2.557 vs. 2.791, <i>P</i> = 0.007; Simpson index: Median 0.168 vs. 0.112, <i>P</i> = 0.004), while the variances were insignificant among HISs with CD4+ T cell counts &gt;300/mm³ (Shannon index: Median 2.981 vs. 2.934, <i>P</i> = 0.179; Simpson index: Median 0.096 vs. 0.119, <i>P</i> = 0.082). Meanwhile, with cART introduction, alterations in the gut microbial composition were more significant in the subgroup with CD4⁺ T cell counts &gt;300/mm³, corresponding to increases in the specific plasma inflammatory markers. These findings implicated the interactive roles of immunodeficiency and cART for affecting gut microbiota in HIV-1-infected individuals, providing new insights into intestinal microbiome dysbiosis related to HIV-1 infection.

免疫缺陷与联合抗逆转录病毒疗法（combined antiretroviral therapy, cART）在塑造HIV-1感染者（HISs）肠道微生物群中的作用，尚未通过时序研究得到全面阐明。本研究纳入36例抗逆转录病毒初治HIV-1感染者，前瞻性评估联合抗逆转录病毒疗法干预后粪便微生物群、反映微生物易位与炎症的血浆标志物的变化。基线时，CD4阳性T细胞计数＜300/mm³的HIV-1感染者，其粪便微生物群的物种α多样性显著低于CD4阳性T细胞计数＞300/mm³的感染者（香农指数：中位数2.557 vs 2.981，*P* = 0.006；辛普森指数：中位数0.168 vs 0.096，*P* = 0.004）。此外，基线α多样性指数与CD4阳性T细胞计数（香农指数：*r* = 0.474，*P* = 0.004；辛普森指数：*r* = −0.467，*P* = 0.004）及特异性血浆微生物易位、炎症生物标志物呈显著相关。启动联合抗逆转录病毒疗法后，CD4阳性T细胞计数＜300/mm³的感染者，其粪便微生物群的物种α多样性得到显著恢复（香农指数：中位数2.557 vs 2.791，*P* = 0.007；辛普森指数：中位数0.168 vs 0.112，*P* = 0.004），而CD4阳性T细胞计数＞300/mm³的感染者组间差异无统计学意义（香农指数：中位数2.981 vs 2.934，*P* = 0.179；辛普森指数：中位数0.096 vs 0.119，*P* = 0.082）。与此同时，启动联合抗逆转录病毒疗法后，CD4阳性T细胞计数＞300/mm³的亚组肠道微生物组成变化更为显著，对应血浆特异性炎症标志物水平升高。本研究结果揭示了免疫缺陷与联合抗逆转录病毒疗法在影响HIV-1感染者肠道微生物群中的交互作用，为HIV-1感染相关肠道微生物群失调提供了新的见解。